Dataset Information

Integrated dataset of screening hits against multiple neglected disease pathogens.

ABSTRACT: New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach.

SUBMITTER: Nwaka S

PROVIDER: S-EPMC3243694 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

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Integrated dataset of screening hits against multiple neglected disease pathogens.

Nwaka Solomon S Besson Dominique D Ramirez Bernadette B Maes Louis L Matheeussen An A Bickle Quentin Q Mansour Nuha R NR Yousif Fouad F Townson Simon S Gokool Suzanne S Cho-Ngwa Fidelis F Samje Moses M Misra-Bhattacharya Shailja S Murthy P K PK Fakorede Foluke F Paris Jean-Marc JM Yeates Clive C Ridley Robert R Van Voorhis Wesley C WC Geary Timothy T

PLoS neglected tropical diseases 20111220 12

New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug disc ...[more]

PMID: 22247786

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Project description:BackgroundThe increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni.Methodology/principal findingsHere we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass) and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths), and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets.Conclusions/significanceUsing the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest novel target candidates that may merit further study, the lists can easily be modified in a user-specific manner, either by adjusting the weights for chosen criteria or by changing the criteria that are included.

Dataset Information

Integrated dataset of screening hits against multiple neglected disease pathogens.

Publications

Integrated dataset of screening hits against multiple neglected disease pathogens.

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